The US Food and Drug Administration's tentative approval process and the global fight against HIV

Abstract

IntroductionIn 2004, the US government began to utilize the Food and Drug Administration's (USFDA) tentative approval process (tFDA) as a basis to determine which HIV drugs are appropriate to be purchased and used in resource‐constrained settings. This process permits products that are not approved for marketing in the US, including medicines with active patents or marketing restrictions in the US, to be purchased and distributed in resource‐constrained settings. Although the tFDA was originally intended to support the United States’ President's Emergency Plan for AIDS Relief (PEPFAR), the USFDA list has become a cornerstone of international HIV programmes that support procurement of ARVs, such as the World Health Organization and the Global Fund to Fight AIDS, Tuberculosis, and Malaria. Our objective in this article is to help the global HIV policy makers and implementers of HIV programmes better understand the benefits and limitations of the tFDA by providing an in‐depth review of the relevant legal and regulatory processes.Discussion USFDA's dedicated tFDA process for ARVs used by the PEPFAR programme has a wide impact globally; however, the implementation and the regulatory processes governing the programme have not been thoroughly described in the medical literature. This paper seeks to help stakeholders better understand the legal and regulatory aspects associated with review of ARVs under the tFDA by describing the following: (1) the tFDA and its importance to global ARV procurement; (2) the regulatory pathways for applications under tFDA for the PEPFAR programme, including modifications to applications, review timelines and costs; (3) the role of US patents, US marketing exclusivity rights, and the Medicines Patents Pool in tFDA; and (4) an overview of how applications for PEPFAR programme are processed through the USFDA. We also provide a case study of a new ARV, tenofovir alafenamide fumarate (TAF), not yet reviewed by USFDA for PEPFAR use.ConclusionsIn this paper, we describe the importance and implementation of USFDA's tentative approval process to review ARVs for resource‐constrained settings. We also highlight the impact of patents and exclusivities on review of HIV drugs under tFDA and illustrate the concepts using a new HIV drug as an example.

Impact of the US Food and Drug Administration registration of antiretroviral drugs on global access to HIV treatment

“…Reliance on the regulatory actions of established stringent regulatory authorities (SRAs) is gaining global momentum as a novel approach to improve timely access to essential, life-saving medicines while saving scarce regulatory resources. 1–4 Under the concept of ‘reliance’, regulatory agencies in resource-constrained settings and entities responsible for procurement may rely on the work already done by SRAs to ensure a source of quality-assured health products. 3–5 Such reliance can enhance regulatory efficiency and contain costs by preventing duplication of efforts and expenditure of limited resources.…”

“…Since 2004, in support of PEPFAR, the USFDA has used a dedicated process to register ARVs to fight HIV globally. 1 11 Under this process, the USFDA can either fully approve a product or issue a tentative approval for a product that may not yet be fully approved in the USA due to patents or market exclusivities, but which meets all safety, efficacy and quality requirements. 1 This process is used to register non-branded versions of ARVs already available in the USA.…”

“… 1 11 Under this process, the USFDA can either fully approve a product or issue a tentative approval for a product that may not yet be fully approved in the USA due to patents or market exclusivities, but which meets all safety, efficacy and quality requirements. 1 This process is used to register non-branded versions of ARVs already available in the USA. 1 Some of the products are new combinations or formulations of existing branded (ie, innovator) drugs, for example, two-drug or three-drug combinations, or paediatric formulations or doses, while others are copies of existing brand name drugs.…”

“… 1 This process is used to register non-branded versions of ARVs already available in the USA. 1 Some of the products are new combinations or formulations of existing branded (ie, innovator) drugs, for example, two-drug or three-drug combinations, or paediatric formulations or doses, while others are copies of existing brand name drugs. 1 Although drug costs are not a factor in the USFDA review or decisions, these non-branded drugs tend to be priced lower than the innovator products, resulting in cost-savings.…”

“… 1 Some of the products are new combinations or formulations of existing branded (ie, innovator) drugs, for example, two-drug or three-drug combinations, or paediatric formulations or doses, while others are copies of existing brand name drugs. 1 Although drug costs are not a factor in the USFDA review or decisions, these non-branded drugs tend to be priced lower than the innovator products, resulting in cost-savings. 12 Such products are placed on a publicly available list and can be procured abroad under PEPFAR, even as domestic sales are precluded.…”